Cds2, also known as CDP-diacylglycerol synthetase-2, is a metabolic enzyme. It controls phosphoinositide recycling by converting phosphatidic acid (PA) to CDP-DG, an essential intermediate in the de novo synthesis of PI [1,2]. This function is crucial for various biological processes, including vascular morphogenesis, lipid metabolism, and cell-specific functions in different tissues [1-4,7,10].

Genetic ablation of Cds2 in endothelial cells switches the output of VEGFA signaling from promoting angiogenesis to inducing vessel regression. In cds2 mutant zebrafish, VEGFA stimulation leads to reverse migration of angiogenic endothelium, and endothelium regression also occurs in postnatal retina and implanted tumor models in mice. In tumor models, CDS2 deficiency enhances tumor-secreted VEGFA, trapping tumors in a VEGFA-induced vessel regression situation, suppressing tumor growth [1]. In primary mouse macrophages, genetic deletion of CDS2 results in increased de novo PA synthesis from G3P, and under sustained GPCR-stimulation of PLC, these macrophages are unable to maintain enhanced rates of PI synthesis via the 'PI cycle' [2]. In liver-specific Cds2-deficient mice, it causes hepatic steatosis, inflammation, and fibrosis, along with impaired mitochondrial function and decreased mitochondrial PE levels [3]. Knockdown of Cds2 in cultured mammalian cells leads to the formation of giant or supersized lipid droplets (LDs), and CDS2 deficiency promotes the LD association of DGAT2 and GPAT4 and impairs initial LD maturation [4,5].

In conclusion, Cds2 plays essential roles in vascular development, lipid metabolism, and mitochondrial function. Gene-knockout and knockdown models, especially in mice, have revealed its significance in tumor growth inhibition, NASH development, and lipid droplet regulation, providing valuable insights into these disease-related biological processes [1,2,3,4,5].